Idiopathic hypereosinophilic syndrome with eosinophilic myositis, peripheral neuropathy and central nervous system involvement

Idiopathic hypereosinophilic syndrome (HES) is a rare disorder marked by a sustained overproduction of eosinophils and a predilection for damage to multiple organ systems. Its neurologic involvement ranges from the central to the peripheral nervous system, and can be associated with eosinophilic myositis. We report a 68-year-old woman who had eosinophilia, eosinophilic dermatitis and eosinophilic pneumonia. She also suffered from numbness and weakness of the lower limbs. Because of long-lasting (> 6 mo) eosinophilia (> 1.5 x 10(9)/L) in the peripheral blood and the fact that no other underlying causes of eosinophilia and neurologic involvement could be identified, a diagnosis of idiopathic hypereosinophilic syndrome was made. The muscle biopsy showed infiltration of inflammatory cells, including a few eosinophils (Liu's stain). Magnetic resonance images, motor evoked potentials, somatosensory evoked potentials and nerve conduction velocities also showed abnormalities in the central and peripheral nervous systems. The pathogenesis and treatments of HES are discussed in this report.     

Identification and chromosomal assignment of two heterozygous mutations in the Trp53 gene in L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cells

Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness and abnormal manifestations of REM sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy is both a significant medical problem and a unique disease model for the study of sleep. Research in human narcolepsy has led to the identification of specific HLA alleles (DQB1*0602 and DQA1*0102) that predispose to the disorder. This has suggested the possibility that narcolepsy may be an autoimmune disorder, a hypothesis that has not been confirmed to date. Genetic factors other than HLA are also likely to be involved. In a canine model of narcolepsy, the disorder is transmitted as a non-MHC single autosomal recessive trait with full penetrance (canarc-1). A tightly linked marker for canarc-1 has been identified, and positional cloning studies are under way to isolate canarc-1 from a newly developed canine genomic BAC library. The molecular cloning of this gene may lead to a better understanding of sleep mechanisms, as has been the case for circadian rhythms following the cloning of frq, per, and Clock.     

Early treatment of posterior retinopathy of prematurity: a controlled trial

OBJECTIVE: The purpose of the study is to assess the possible benefits of early laser treatment for posterior retinopathy of prematurity (ROP) and to provide data concerning the natural history of posterior ROP. DESIGN: The study design was a prospective, multicenter, randomized trial. PARTICIPANTS: A total of 19 infants with prethreshold posterior ROP were studied. INTERVENTION: Randomization to immediate indirect laser photocoagulation or observation, with application of laser photocoagulation for those control eyes reaching threshold disease, was performed. MAIN OUTCOME MEASURES: Patients were assessed at 3 months and the anatomic outcome recorded along with any adverse treatment effects. RESULTS: An unfavorable structural outcome developed in 3 (16%) of 19 early treatment eyes compared with 3 (18%) of 17 for those treated only if threshold disease was reached. Of the 17 control eyes, 15 (88%) reached threshold disease. Progression to threshold occurred within 1 week in all but two eyes. All 12 control eyes with posterior ROP and any amount of extraretinal fibrovascular proliferation progressed to threshold disease. CONCLUSIONS: Although the number of patients studied is too small to reach statistical significance, the likelihood of a favorable outcome for eyes with prethreshold posterior ROP treated immediately with laser photocoagulation is comparable to that obtained by withholding treatment until threshold disease is reached. There is a high probability of progression from prethreshold to threshold disease, usually within 1 week or less.     

A filtration method for improving film dosimetry in photon radiation therapy

Successful radiotherapy requires accurate dosimetry for treatment verification. Existing dosimeters such as ion chambers, TLD, and diodes have drawbacks such as relatively long measurement time and poor spatial resolution. These disadvantages become serious problems for dynamic-wedged beams. Thus the clinical use of dynamic wedges requires an improved dosimetry method. X-ray film may serve this purpose. However, x-ray film is not clinically accepted as a dosimeter for photon beams, because it overresponds to photons with energies below about 400 keV. This paper presents and develops a method which was initially proposed by Burch to improve the dose response of x-ray film in a phantom. The method is based on placing high-atomic number foils next to the film. The foils are used as filters to preferentially remove low-energy photons. The optimal film and filter configuration in a phantom was determined using a mathematical scheme derived in this study and a Monte Carlo technique (ITS code). The optimal configuration thus determined is as follows: the filter-to-film distance of 6 mm and the filter thickness of 0.15 mm for percent depth-dose measurement; the distance of 1 cm and the thickness of 0.25 mm for off-axis (dose) ratio measurement. The configuration was then tested with photon beams from a 4 MV linac. The test result indicates that the in-phantom dose distribution based on the optimal configuration agrees well with those measured by ion chambers.     

Is there evidence for an age-related reduction in metabolic rate?

To determine whether the age-related reduction in basal metabolic rate (BMR) is explained by a quantitative and/or qualitative change in the components of lean tissue, we conducted a cross-sectional study in groups of young (n = 38, 18-35 yr) and older (n = 24, 50-77 yr) healthy individuals. BMR was measured by indirect calorimetry. Body composition was obtained by using dual-energy X-ray absorptiometry (DEXA), which permitted four compartments to be quantified [bone mineral mass, fat mass (FM), appendicular lean tissue mass (ALTM), and nonappendicular lean tissue mass (NALTM)]. Absolute BMR and ALTM were lower, whereas FM was significantly higher in the older, compared with young, subjects. BMR, adjusted for differences in FM, ALTM, and NALTM, was significantly lower in the older subjects by 644 kJ/day. In separate regression analyses of BMR on body compartments, older subjects had significantly lower regression coefficients for ALTM and NALTM, compared with young subjects. Hence, the age-related decline in BMR is partly explained by a reduction in the quantity, as well as the metabolic activity, of DEXA-derived lean tissue components.     

Development and comparison of assays for measuring immunospecific antibody response in serum of chickens and rabbits immunized with human immunoglobulin G

The antibody response development during polyclonal antibody production is a relevant parameter to monitor during the immunization period to be able to optimize the immunization protocol and to determine the optimal antibody harvest time. Although rabbits and other mammals are most often used for polyclonal antibody production, the chicken is a relevant alternative. There are both scientific reasons, economic reasons, and animal welfare reasons to consider when choosing the chicken instead of a mammal for this purpose, because antibodies in generous quantities can be harvested from the egg yolk. This study compared different assays for measuring antibody response in rabbit and chicken serum. An inhibition liquid phase absorption assay (ILPAA), a rocket immunoelectrophoresis (RIE) assay, and a line immunoelectrophoresis (LIE) assay were compared to ELISAs. The ELISA proved to be the most useful assay for routine use, as it was less time-consuming and because the assay could easily be adapted to both serum antibody types. However, electrophoretic assays were the most useful as combined analytical and quantitative tools and must be considered essential when analyzing specificities of polyclonal antibody preparations.     

Catecholamine secretion from bovine adrenal chromaffin cells: the role of the Na+/Ca2+ exchanger and the intracellular Ca2+ pool

The role of the Na+/Ca2+ exchanger and intracellular nonmitochondrial Ca2+ pool in the regulation of cytosolic free calcium concentration ([Ca2+]i) during catecholamine secretion was investigated. Catecholamine secretion and [Ca2+]i were simultaneously monitored in a single chromaffin cell. After high-K+ stimulation, control cells and cells in which the Na+/Ca2+ exchange activity was inhibited showed similar rates of [Ca2+]i elevation. However, the recovery of [Ca2+]i to resting levels was slower in the inhibited cells. Inhibition of the exchanger increased the total catecholamine secretion by prolonging the secretion. Inhibition of the Ca2+ pump of the intracellular Ca2+ pool with thapsigargin caused a significant delay in the recovery of [Ca2+]i and greatly enhanced the secretory events. These data suggest that both the Na+/Ca2+ exchanger and the thapsigargin-sensitive Ca2+ pool are important in the regulation of [Ca2+]i and, by modulating the time course of secretion, are important in determining the extent of secretion.